Rapamycin a macrocyclic lactone has been shown to have antitumor activity (U.S. Pat. No. 4,885,171). The biological effects of rapamycin are reviewed in Transplantation Reviews, 1992, 6, 39–87. Semisynthetic analogs of Rapamycin are described in WO 95/14023 and further described in WO 93/16189 are macrocyclic lactones produced by the cultures Streptomyces hygroscopicus (FERM BP-3688), Actinoplanes sp. (FERM BP-3832) or Streptomyces toyocaensis subsp.humicola (ATCC 39471) to produce macrocyclic lactones of the formula
Additional Rapamycin analogs produced by fermentation means described in the art include: 7,29-bisdesmethyl-rapamycin (U.S. Pat. No. 5,093,338); 16-nor-rapamycin (WO 94/10843); 14-methylene rapamycin and 9-methylene rapamycin (WO 93/11130); 7,42-bis (O-demethyl)rapamycin (WO 94/18208) and a process to produce 7-O-dimethylrapamycin by cultivating ATCC 55368.
Microbial desmethylation of FK506/FR900520 by actinoplanes sp. ATCC 53771 forming products with immunosuppressive activity is reported by Tom S. Chen, et al., The Journal of Antibiotics, 45, 118–123 (1992).
Rapamycin structures formed by microbial manipulations of Actinoplanes sp. N902-109 are described by Hiroyuki Nishida, et al., The Journal of Antibiotics, 48, 657–666 (1995).
The precursor feedings and fermentation of s. hygroscopicus LEK III and the ability to synthesize rapamycins is reported by Lake II Khaw, et al., Journal of Bacteriology, 180, 809–14 (1998).
New antitumor compounds are continually in demand, for the treatment of cancer in man and the production of new macrolide anticancer compounds by fermentation means is an important feature of developing antitumor agents for further studies. Equally important are novel strains of cultures used in the production processes for preparing these compounds.